Heterocyclic
amines (HCAs) are formed when meat products such as beef, chicken, pork and fish
are cooked at high temperatures. The most abundant HCA found in the human diet
is PhIP causes mammary carcinomas in female rats and mice, and is associated
with an increased risk of developing colon, breast, and prostate cancer in
humans. PhIP is metabolized by cytochrome P-450s producing N-OH-PhIP. The
N-OH-PhIP can be esterified by phase II enzymes forming an arylnitrenium ion
that binds to DNA causing adducts. Furthermore, N-OH-PhIP may be reduced by
cytochrome b5 reductase producing superoxide anions and hydroxyl radicals
causing DNA strand breaks. Diallyl sulfide (DAS) has been shown to prevent
cancer in several animal models, presumably by metabolic modulation. We
hypothesize that PhIP produces reactive oxygen species causing DNA strand breaks
and that DAS will inhibit the formation of PhIP induced DNA strand breaks. To
test this hypothesis we treated normal breast epithelial (MCF-10A) cells with
PhIP, DAS and a combination of PhIP and DAS. The detection of lipid peroxides
was used as a surrogate for ROS. Lipid peroxides were detected using a
PeroxiDetect kit (Sigma). PhIP increased the production of lipid peroxides and
DAS decreased the PhIP-induced peroxidation by 47%. To determine if PhIP causes
DNA strand breaks in MCF-10A cells, cells were treated for 3, 6, 9, and 24 h
with PhIP (100 microM), DAS (100 microM) and a combination of PhIP (100 microM)
and DAS (100 microM). DNA strand breaks were evaluated using the Comet assay.
PhIP produced DNA strand breaks in a dose- and time-dependent fashion. We have
shown that DAS inhibits PhIP-induced DNA strand breaks by inhibiting the
production of reactive oxygen species. Therefore, we propose that DAS can
prevent PhIP-induced breast cancer.

Obesity, Diet and Risk of
Non-Hodgkin Lymphoma.

Division of
Environmental Health Sciences, School of Public Health, 140 Earl Warren Hall
University of California, Berkeley, California.

Non-Hodgkin
lymphoma (NHL) represents a group of heterogeneous diseases that significantly
vary in their causes, molecular profiles, and natural progression. In 2007,
there will be approximately 59,000 newly diagnosed NHL cases in the United
States and over 300,000 cases worldwide. Although new therapeutic regimens are
minimizing the number of deaths related to NHL, causes for the majority of
lymphomas remain undetermined. Recent studies suggest that dietary factors may
contribute to the rising rates of NHL. This review will summarize epidemiologic
reports that have studied the relationship between obesity, physical activity,
and diet and risk of NHL. Based on a number of case-control and prospective
cohort studies, overweight/obesity probably increases the risk of NHL, whereas
moderate physical activity may reduce risk. Several studies support an inverse
association between intakes of vegetables and NHL risk, particularly for the
consumption of cruciferous vegetables. This may relate to the induction of
apoptosis and growth arrest in preneoplastic and neoplastic cells, two important
actions of isothiocyanates found in cruciferous vegetables. Studies also suggest
that fish intake may be inversely associated with risk of NHL, although findings
have not been entirely consistent. This may relate to the high organochlorine
content in some fish that could override a protective effect. High consumption
of fats, meat, and dairy products also may increase lymphoma risk. The
accumulated scientific evidence concerning the associations between obesity,
diet, and NHL suggests several identified modifiable risk factors that might be
recommended to decrease lymphoma risk. (Cancer Epidemiol Biomarkers Prev
2007;16(3):392-5).

OBJECTIVE: To
evaluate the association of meat and dairy food consumption with subsequent risk
of prostate cancer. METHODS: In 1989, 3,892 men 35+ years old, who participated
in CLUE II study of Washington County, MD, completed an abbreviated Block food
frequency questionnaire. Intake of meat and dairy related foods was calculated
using consumption frequency and portion size. Incident prostate cancer cases (n
= 199) were ascertained through October 2004. Cox proportional hazards
regression was used to calculate hazard ratios (HR) of total and advanced (SEER
states three and four; n = 54) prostate cancer and 95% confidence intervals (CI)
adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato
products. RESULTS: Intakes of total mean (HR = 0.90, 95% CI 0.60-1.33, comparing
highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not
statistically significantly associated with prostate cancer. However, processed
meat consumption was associated with a non-statistically significant higher risk
of total (5+ vs. < or =1 servings/week: HR = 2.24; 95% CI 0.90-5.59) prostate
cancer. There was no association across tertiles of dairy or calcium with total
prostate cancer, although compared tp < or =1 servings/week consumption of 5+
servings/week of dairy foods was associated with an increased risk of prostate
cancer (HR = 1.65, 98% CI 1.02-2.66). CONCLUSION: Overall, consumption of
processed meat, but not total meat or red meat, was associated with a possible
increased risk of total prostate cancer in this prospective study. Higher intake
of dairy foods but not calcium was positively associated with prostate cancer.
Further investigation into the mechanisms by which processed meat and dairy
consumption might increase the risk of prostate cancer is suggested.

Prevention and early detection
of colorectal cancer--new horizons. Rennert G.

Colorectal
cancer is potentially one of the most preventable malignancies. Nutritional
awareness (low fat, low red meat, high fruits and vegetables) and regular
physical activity have major potential for primary prevention of this
malignancy, while early detection technologies have the potential of both
influencing mortality from colorectal cancer as well as enhancing primary
prevention through detection and removal of lesions that could potentially
develop into cancer. While the potential for prevention is large, its
materialization is far from being optimal. The large-scale lifestyle changes in
the population necessary to reduce colorectal cancer rates are hard to achieve,
and most of the early detection technologies are either invasive or otherwise
nonappealing to the population. Thus, without abandoning the proven prevention
methods, new avenues need to be investigated to deal with this malignancy, which
carries both high morbidity and high mortality. Such new avenues can now be
followed, both in prevention and detection. Chemoprevention, or the use of
medications to prevent disease, has now been extensively explored in colorectal
cancer. Some of these interventions, such as supplemental fibers, have failed to
demonstrate the anticipated effect, while others such as calcium supplementation
have been shown to reduce formation of premalignant lesions, polyps, or
adenomas. Data accumulating in recent years have suggested that aspirin,
nonsteroidal anti-inflammatory drugs, and selective COX-II inhibitors all have a
potential to reduce both colorectal cancer and colorectal adenomas. Issues of
safety and therapeutic indexes have recently come up as barriers to the use of
COX-II inhibitors, and have again drawn attention to aspirin as a potential drug
of choice. Association studies have also shown a major potential role for
statins in colorectal cancer prevention. New methodologies in cancer detection
involve the introduction of colonography or virtual colonoscopy, and the
development of methods of detection of genetic somatic mutations in feces or
peripheral blood. While radiological techniques currently avoid the need for
premedication and are less invasive, they currently still require similar gut
cleansing to colonoscopy, can also lead to perforation, are costly, and carry a
non-negligible exposure to radiation. Genetic analysis of the stool for
mutations in tumor cells is evolving as a promising technique, struggling to
achieve both high sensitivity and high specificity with the right combination of
mutations sought. With all of these developments taking place, the near future
will undoubtedly bring about the expected reduction in colorectal cancer
mortality.

Objective:To
compare fracture rates in four diet groups (meat eaters, fish eaters,
vegetarians and vegans) in the Oxford cohort of the European Prospective
Investigation into Cancer and Nutrition (EPIC-Oxford).Design:Prospective cohort
study of self-reported fracture risk at follow-up.Setting:The United
Kingdom.Subjects:A total of 7947 men and 26 749 women aged 20-89 years,
including 19 249 meat eaters, 4901 fish eaters, 9420 vegetarians and 1126
vegans, recruited by postal methods and through general practice
surgeries.Methods:Cox regression.Results:Over an average of 5.2 years of
follow-up, 343 men and 1555 women reported one or more fractures. Compared with
meat eaters, fracture incidence rate ratios in men and women combined adjusted
for sex, age and non-dietary factors were 1.01 (95% CI 0.88-1.17) for fish
eaters, 1.00 (0.89-1.13) for vegetarians and 1.30 (1.02-1.66) for vegans. After
further adjustment for dietary energy and calcium intake the incidence rate
ratio among vegans compared with meat eaters was 1.15 (0.89-1.49). Among
subjects consuming at least 525 mg/day calcium the corresponding incidence rate
ratios were 1.05 (0.90-1.21) for fish eaters, 1.02 (0.90-1.15) for vegetarians
and 1.00 (0.69-1.44) for vegans.Conclusions:In this population, fracture risk
was similar for meat eaters, fish eaters and vegetarians. The higher fracture
risk in the vegans appeared to be a consequence of their considerably lower mean
calcium intake. An adequate calcium intake is essential for bone health,
irrespective of dietary preferences.Sponsorship:The EPIC-Oxford study is
supported by The Medical Research Council and Cancer Research UK.European
Journal of Clinical Nutrition advance online publication, 7 February 2007;
doi:10.1038/sj.ejcn.1602659.

Environmental Epidemiology Unit, University of Southampton, Southampton General
Hospital, UK.

Routine
statistics of occupational mortality and incidence of cancer have consistently
shown high rates of lung cancer in butchers. Possible explanations include
infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic
hydrocarbons and nitrites in the preservation of meat, or a confounding effect
of tobacco. To explore these possibilities, we have examined the mortality of
1610 men employed at three British companies processing pork, beef, lamb, bacon,
and other meat products. The overall death rate was less than in the national
population (271 deaths observed, 310 expected) but there was an excess of deaths
from cancer (87 observed, 80 expected), and in particular from lung cancer (42
observed, 32 expected). The risk of lung cancer was concentrated in subjects
exposed to recently slaughtered meat, especially after an interval of 10 or more
years. These findings increase suspicions of a risk of lung cancer in butchers,
although further information is needed about smoking habits in the meat
industry. If there is a hazard infection by a papilloma virus would seem the
most likely cause.

September/October
2006

An Update of
Broward County Air Licensing for Remediation Systems

An Official
Bimonthly Publication of Broward County’s

Environmental
Protection Department

Polycyclic
aromatic hydrocarbons, commonly referred to as PAHs, are carcinogenic organic
molecules consisting of three or

more rings
containing carbon and hydrogen which are a by-product of fossil fuel combustion.
PAHs are also by-products of

incomplete
burning of organic substances such as tobacco and charbroiled meat.
Common sources of PAHs are asphalt for

Division of
Cancer Epidemiology and Genetics, National Cancer Institute, Department of
Health and Human Services.

Red and
processed meat intake is associated with increased risks of both colorectal
adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of
N-nitroso compounds (NOC); furthermore, meats cooked at high-temperatures
contain heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH).
Specific NOC, HCA, and PAH are mutagens and animal carcinogens. We conducted a
case-control study of 146 cases of colorectal adenoma, diagnosed at
sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds
ratios (and 95% confidence intervals) and found a 2-fold increased risk in the
highest, compared to the lowest, quartile of processed meat intake (95% CI =
1.0-4.0). We estimated nitrate and nitrite intake from meat using published data
from the literature as well as from actual measurements of meats analyzed
recently. We evaluated the interaction of processed meat and nitrate plus
nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to
their carcinogenic form. Results for both methods of estimating nitrate and
nitrite intake were similar; compared with the lowest, the highest quartile was
associated with a two-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the
HCA MeIQx attenuated the association (OR=1.6, 95% CI = 0.8-3.2), but other HCA
and a PAH had minimal effect. Higher CYP2A6 activity was not associated with
risk and there was no evidence of an interaction between CYP2A6 activity with
nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake
from processed meat intake increases the risk of colorectal adenoma after
accounting for HCA and PAH.

Consumption of
charbroiled red meat and meat-derived polycyclic aromatic hydrocarbons (PAHs)
has been associated with risk of colorectal adenoma, a precursor of colorectal
cancer. Furthermore, leukocyte PAH-DNA adduct levels have been demonstrated to
increase in response to charbroiled red meat intake but to date there have been
no studies that have investigated the relationship between leukocyte PAH-DNA
adduct levels and risk of colorectal adenoma. We investigated the relation of
leukocyte PAH-DNA adduct formation and colorectal adenoma in a clinic-based
case-control study of colorectal adenomas. The study comprised 82 cases of
colorectal adenoma and 111 polyp-free controls, none of whom were current
smokers. Leukocyte PAH-DNA adducts were measured by a sensitive
chemiluminescence immunoassay (CIA) using an antiserum elicited against DNA
modified with
(+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene
(BPDE) that recognizes several PAHs bound to human DNA. Leukocyte PAH-DNA adduct
levels were higher among colorectal adenoma cases (median, 1.4 adducts per 10(8)
nucleotides) than polyp-free controls (median, 1.2 adducts per 10(8)
nucleotides) (P = 0.02). There was a positive association between PAH-DNA adduct
level and adenoma prevalence: each unit increase in PAH-DNA adduct level (per
10(8) nucleotides) was associated with an odds ratio of 1.5 (95% confidence
interval [CI], 1.1-2.2). In addition, a comparison of the lowest quartile for
PAH-DNA adduct level with the highest quartile yielded an odds ratio of 2.8
(95%CI, 1.2-6.5; P(trend) = 0.048) for risk of colorectal adenoma. These data
support a link between PAH exposure and colorectal adenoma.